S223: LATE CARDIOVASCULAR TOXICITY AFTER HIGH-DOSE CHEMOTHERAPY FOR LYMPHOMA: A DANISH POPULATION-BASED STUDY
Authors: S. Husby, J. Baech, T. Trab, J. Gørløv, J. M. Jørgensen, S. Gudbrandsdottir, M. T. Severinsen, K. Grønbæk, T. S. Larsen, P. Brown, L. H. Jakobsen, K Kragholm, T. C. El-Galaly
Journal: HemaSphere (2022)

Background: Salvage chemotherapy followed by high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) are standard treatments for younger patients with relapsed/refractory aggressive diffuse large B-cell lymphoma (DLBCL) and Hodgkin’s lymphoma (HL) as well as for consolidation in 1st line treatment for mantle cell lymphoma (MCL) and peripheral T-cell lymphoma (PTCL). Congestive heart failure (CHF) is a known late complication to lymphoma therapy, but it is unclear how much HDT adds to CHF risk. Delineating late complications to HDT/ASCT is increasingly important due to the availability of alternatives such as CAR-T therapy. Aims: To investigate how HDT/ASCT treatment influences the risk of developing congestive heart failure in a population-based nationwide setting. Methods: Data were obtained from the nationwide Danish lymphoma registry and the Danish National Patient Register. DLBCL, MCL, HL, and PTCL patients treated with HDT between 2001 and 2017 and without CHF prior to HDT were included. Patients were compared to two populations: 1) A matched population of individuals from the general population without prior CHF matched on age and sex in a 1:5 ratio, and 2) A population of lymphoma patients (HL or DLBCL) in clinical remission two years after standard 1st line treatment without HDT. The latter group was chosen due to very low lymphoma-specific mortality. CHF was defined by ICD-10 outpatient clinic and hospital discharge diagnosis codes. The Aalen-Johansen estimator was used to compute the cumulative risks treating death as competing event. This analysis was conducted for CHF and cardiovascular diseases in general, separately (CVD; ischemic heart disease, atrial fibrillation/flutter, ventricular fibrillation/flutter, and CHF). Crude and adjusted cause-specific hazard ratios (HR) were obtained using Cox regression and adjustments were made for age and sex. Results: A total of 958 HDT patients were identified (35% DLBCL, 28% MCL, 21% PTCL, and 16% HL) with a median follow-up of 7.9 years. Almost all patients were previously treated with anthracycline (97.8%). The risk of both CHF and CVD was significantly increased in patients treated with HDT compared to a matched background population (p<0.001; Fig. 1a, 1b). The risk of CHF was more pronounced in HDT-treated males compared to females (10-year incidence 7.8% vs 3.8%, respectively, Fig. 1c and Fig. 1d); however, the risk was significantly increased for both sexes (p<0.001 for both). Multivariable Cox regression adjusted for sex and age confirmed the increased risk of CHF for HDT patients. The risk was increased both when compared to the matched background population (adjusted HR 6.40) and to lymphoma patients not treated with HDT (adjusted HR 2.54). This is intriguing since HDT patients are generally considered more fit than unselected lymphoma patients. Comparison of comorbidities between the groups is ongoing. In the HDT group, the major risk factors for CHF were older age at the time of HDT (HR 1.20 per decade), and male sex (HR 2.15). Image:Summary/Conclusion: The risk of CHF and CVD in general is significantly increased for HDT treated patients compared to both a matched background population and patients treated with 1st line therapy without consolidating HDT, despite likely selection of healthy patients to HDT. Major risk factors were male sex and age. These findings are important when considering the possible use of new therapies such as CAR-T cell therapy which have a different safety profile.